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  • Title: A novel 99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study.
    Author: Zhao Q, Yan P, Wang RF, Zhang CL, Li L, Yin L.
    Journal: PLoS One; 2013; 8(4):e61043. PubMed ID: 23573294.
    Abstract:
    INTRODUCTION: Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether (99m)Tc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis. METHODS: The RRL peptide was designed and radiosynthesized with (99m)Tc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. (99m)Tc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of (99m)Tc-RRL was also explored. RESULTS: The labeling efficiencies of (99m)Tc-RRL reached 76.9% ± 4.5% (n = 6) within 30-60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that (99m)Tc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of (99m)Tc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2-6 h after injection of (99m)Tc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with (99m)Tc-RRL was comparable with that of (18)F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of (99m)Tc-RRL with R(2) = 0.821. CONCLUSION: (99m)Tc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas.
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